P1324: EFFICACY AND SAFETY OF DOSE-ADJUSTED ATG COMBINED WITH CD25 ANTIBODY IN THE PREVENTION OF GVHD AFTER HAPLO-HSCT: CLINICAL STUDY DATA FROM A SINGLE CENTER IN CHINA
Authors: Lidan Zhu, Jia Liu, Shichun Gao, Lu Wang, Huanfeng Liu, Peiyan Kong, Ting Chen, Yimei Feng, Han Yao, Yuqing Liu, Lu Zhao, Lei Gao, XI Zhang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the most effective method for curing a variety of hematologic malignancies, haploidentical donors have been increasingly considered for transplantation in patients without HLA matched donors. However, graft-versus-host disease (GVHD) is one of the most common complications after allo-HSCT, especially severe in haploidentical HSCT (haplo-HSCT), therefore, exploring an optimal GVHD prevention strategy is unmet need. Aims: To figure out the safety and efficacy of combination dose-adjusted ATG (7.5mg/kg) and anti-CD25 antibody in preventing GVHD，infection and disease relapse after haplo-HSCT. Methods: From December 2020 to December 2022, 42 patients (pts) in our center who underwent haplo-HSCT for a variety of hematologic diseases were enrolled in this study. All patients received combination dose-adjusted ATG and anti-CD25 antibody as follows: 34 pts received conditioning regimen with Me-CCNU+Ara-C+BU+CY+ATG+CD25 (smostomatine 0.2g/m2×1d, busulfan 0.8mg/kg q6h×3d, cyclophosphamide 1.8g/m2×2d, cytarabine 2g/m2 q12h×2d, ATG 2.5mg/kg×3d, CD25 monoclonal antibody 1mg/kg×1d), and 8 pts were given G-CSF+decitabine+Me-CCNU+Ara-C+BU+CY+ATG+CD25 regimen (G-CSF: 300ug×6d, decitabine 20mg/m2×5d, busulfan 0.8mg/kg q6h×3d, cyclophosphamide 1.8g/m2×2d, cytarabine 2g/m2 q12h×2d, ATG 2.5mg/kg×3d, CD25 monoclonal antibody 1mg/kg ×1d). The short-course tacrolimus (FK506) + methotrexate (MTX) + mycophenolate mofetil (MMF) regimen was administered to prevent GVHD. Results: Among the 42 patients, 19 were females, and 23 were males, with a median age of 35 (13-58) years. The median time of neutrophil recovery was 16 (10-27) days, and the time for platelet reconstitution was 18 (11-33) days. All patients were 100% complete donor engraftment, and 5 patients occurred secondary implantation dysfunction, when treated with umbilical cord MSCs and TPO-RA, the 5 patients had complete engraftment. During the follow up, 24 pts occurred fever with only 7 pts had been found evidence of etiology, four pts were bacterial infections, one was fungal infection, one was a stool culture bacterial infection, one was a urinary culture bacterial infection, and the remaining 14 pts were agranulocytosis with fever. 18 patients (42.8%) had cytomegalovirus (CMV) infections, which was obvious lower than previous report of our center, the median time was 41 (20-66) days, only 2 pts were diagnosed as retinitis and retinal necrosis, with anti-virus treatment, the patients were recovery. Among the 42 patients, 14 pts (33.3) developed acute GVHD with grade I-II aGVHD, and 2 pts was observed grade III-IV aGVHD, the medium time of aGVHD occurred was 48.5 (21-91) days, which was significantly lower compared with our previous results (53.5%). 11 patients (26.2%) developed chronic GVHD (cGVHD), the medium time was 117.5 (104-188) days, no significantly difference was observed compared with our previous results (23.2%). Medium followed up was 294(32-499) days, only 1 patient died with uncontrolled infection, and 1 patient died with intracranial hemorrhage and TMA. Three relapsed patients received system therapy strategy with CART, DLI, demethylating drugs and immunomodulators achieved complete remission again. Summary/Conclusion: Combination of dose-adjusted ATG (7.5mg/kg) and anti-CD25 antibody strategy could decrease the occurrence of GVHD, without increase of severe infection and risk of disease relapse. Limited to the retrospective and small scale, future prospective and controlled studies are needed to further investigate the efficacy of this treatment on haplo-HSCT. Keywords: Acute graft-versus-host disease, ATG